PPP2R5B

Chr 11

protein phosphatase 2 regulatory subunit B'beta

Also known as: B56B, B56beta, PR61B

NCBI Gene: 5526 ENSG00000068971 UniProt: Q15173

The protein functions as a regulatory B56β subunit of protein phosphatase 2A, modulating substrate selectivity and catalytic activity of this major serine/threonine phosphatase that negatively controls cell growth and division. De novo mutations in PPP2R5B cause a neurodevelopmental disorder with intellectual disability, seizures, and variable dysmorphic features, following an autosomal dominant inheritance pattern. The pathogenic mechanism involves haploinsufficiency, as indicated by the gene's extreme intolerance to loss-of-function variants.

ResearchSummary from RefSeq, UniProt

The product of this gene belongs to the phosphatase 2A regulatory subunit B family. Protein phosphatase 2A is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The B regulatory subunit might modulate substrate selectivity and catalytic activity. This gene encodes a beta isoform of the regulatory subunit B56 subfamily. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.30

LOEUF· LoF intol.

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.30LOEUF

pLI 0.984

Z-score 4.16

OE 0.12 (0.05–0.30)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.46Z-score

OE missense 0.60 (0.53–0.68)

182 obs / 302.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.12 (0.05–0.30)

0≤0.351.4

Missense OE?0.60 (0.53–0.68)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 3 / 25.8Missense obs/exp: 182 / 302.5Syn Z: 0.36

Background carrier burden — how many people carry a rare variant somewhere in PPP2R5B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 170

476 rare PASS variants

Rare truncating (LoF)

1 in 3,900

67 rare PASS variants

Rare synonymous (reference)

1 in 240

294 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PPP2R5B. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 200	1 in 6,400
South Asian	~43k	1 in 120	1 in 1,700
Remaining (unassigned)	~30k	1 in 180	1 in 4,900
European (Finnish)	~27k	1 in 210	≈ 1 in 13,000
Admixed American	~22k	1 in 170	1 in 1,200
African / African American	~21k	1 in 160	1 in 2,000
East Asian	~20k	1 in 140	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 810	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 390	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 13 coding exons well covered in gnomAD exomes and genomes.? see exons ↓